Islet Xenotransplantation: Are We Really Ready for Clinical Trials?

Four clinical trials of porcine islet transplantation have been reported, and there are verbal reports that clinical trials on much larger scales are continuing in centers in China and Russia. The four reported trials are briefly reviewed and, in the light of the present status of experimental islet xenotransplantation, consideration is given to whether such trials are currently justified. The Ethics Committee of the International Xenotransplantation Association has (1) emphasized the need for encouraging studies in non-human primates before clinical trials should be undertaken, (2) mandatory monitoring for the transfer of porcine microorganisms, and (3) careful regulation and oversight by recognized bodies. Other aspects of the topic, such as the need for informed consent, are briefly discussed. We conclude that, at the present time, more data documenting convincing efficacy, focused on clinically applicable immunosuppressive regimens, are needed to justify the initiation of closely monitored clinical trials. A clinical trial may then be justified even though the potential risk to the patients, and possibly for society, will not be zero.     

Effects of labeling and treatment of hypertension on perceived health

The effects of labeling a person as hypertensive have important implications for hypertension screening. The Hypertension Detection and Follow-up Program (HDFP) provides an opportunity to examine the effects of labeling, treatment, and study assignment on a large group of hypertensives (n = 10,070). Their answers to questions regarding perceived health and general well-being asked at baseline and again one year later were analyzed. There was no significant change in the perceived health status of persons who were unaware of their hypertension at baseline and remained untreated at one year (labeling alone). The effect of labeling plus treatment was associated with a significant decrease in perceived health. The effect of antihypertensive drug therapy on perceived health status was examined in persons who were aware of their hypertension but not on treatment at baseline, and on treatment at one year. The stepped care group (SC) had a significant improvement in their perceived health and a significant decrease in the amount of time spent worrying about their health. The referred care group (RC) had no change. Program assignment effects were studied in individuals aware of their hypertension and on treatment both at baseline and one year later. Both the SC and RC groups had a significant improvement in their perceptions of their health status. The SC group had a significant decrease in time spent worrying about their health, while the RC group showed no change. These reassuring results fail to support the suggestion that labeling persons as hypertensive is necessarily followed by negative psychological consequences.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxford Handbook of Pre-hospital Care

There are at least two reasons why this Oxford handbook meritsa review in the British Journal of Anaesthesia. A proportionof readers will be involved at some time during their careerin the provision of pre-hospital care and most of us will onoccasion manage patients on their arrival in hospital followingcare for acute medical and surgical problems in the community.The Oxford series aims to act as a succinct primer in each subject,and this one succeeds. The contents page illustrates its     

Evidence of sustained skeletal benefits from impact-loading exercise in young females: a 3-year longitudinal study.

The skeletal effects from intensive exercise throughout puberty are undefined. Forty-five female gymnasts and 52 controls were studied over 3 years, including a heredity aspect. The effects of size, maturity, exercise, and diet were identified using a multilevel regression model. Results demonstrated sustained skeletal benefits resulting from exercise throughout all stages of pubertal development. INTRODUCTION: Weight-bearing exercise is beneficial for peak bone mass development. However, whether skeletal benefits achieved with exercise are maintained if training remains intensive throughout the pubertal years is not entirely clear. The influence of familial resemblance for bone mass remains undefined in physically active versus inactive children. The aim of this study was to investigate the long-term influences of impact-loading exercise on bone quantity and quality in young females after controlling for growth, maturation, and hereditary factors. MATERIALS AND METHODS: At baseline, 45 gymnasts (G) and 52 normally active controls (C) 8-17 years of age were recruited. Anthropometry, diet, physical activity, and quantitative ultrasound (QUS) were measured annually for 3 consecutive years. DXA scans of total body (TB) and lumbar spine (LS) bone mineral content (BMC) and density (BMD) were taken three times at 1-year intervals. A multilevel regression model was fitted, and the independent effects of body size, maturity, physical activity, and diet were identified over time. To assess heredity influences, 27 G mothers and 26 C mothers volunteered for cross-sectional measurements of anthropometry, QUS, and BMC/BMD. RESULTS AND CONCLUSIONS: Gymnasts were smaller and lighter (as were their mothers) than controls, but they had significantly higher QUS and axial and appendicular BMC and BMD, with > 170 g more bone mineral in TB across puberty (after adjustment for maturity [years from peak height velocity], height, weight, energy, and protein intake). Gymnasts had up to 24-51% higher BMC and 13-28% higher BMD, depending on skeletal site. These results provide evidence of sustained skeletal benefits from impact-loading exercise, which are unlikely to result entirely from heredity, throughout pubertal years.     

Early pharmacokinetics and clinical effects of oral D-amphetamine in normal subjects

Seven normal subjects received 0.25 mg/kg D-amphetamine orally, both after an overnight fast and again after a standard breakfast. Plasma levels, subjective and cardiovascular effects, and observer-rated activation were assessed hourly for 5 hr. Food did not affect amphetamine levels. Plasma levels peaked at 2-3 hr. Maximum cardiovascular effects generally occurred at 1 hr, whereas maximum behavioral and subjective effects occurred at 2 hr. Subjective and behavioral effects declined thereafter, in spite of substantial amphetamine levels. A separate group of 8 subjects received 0.5 mg/kg D-amphetamine orally. Plasma levels, subjective and cardiovascular effects, and activation ratings were assessed hourly for 4 hr. Maximum plasma levels were approximately twice those seen in the first group. In this case, plasma levels peaked at 3-4 hr; blood pressure and subjective and behavioral effects were all maximal at 2-3 hr and were declining by 4 hr, in spite of stable or rising plasma levels.     

A phase I/II study of continuous infusion suramin in patients with hormone-refractory prostate cancer : toxicity and response

 Introduction: Suramin is a synthetic polysulfonated naphthylurea which has been used for the treatment of African trypanosomiasis and onchocerciasis, but since the mid-1980s has received attention as a possible antiretroviral and antineoplastic agent. Objective: This clinical trial of suramin was undertaken as a phase I/II study in patients with hormone-refractory prostate cancer, with the hypothesis that the intensity of therapy with suramin could be increased significantly if measures were undertaken to maintain the plasma concentrations of the drug under 300 μg/ml. Methods: We report the clinical results of this trial, wherein patients were treated at three different targeted plasma suramin concentrations (275, 215 and 175 μg/ml) for varying periods of time (2, 4 or 8 weeks), with delivery of the drug by continuous intravenous infusion. Results: The major toxicity observed in this trial was neurologic, consisting of a motor and sensory peripheral neuropathy that resulted in both paresis and paralysis of the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was observed in the patients treated at a plasma suramin concentration of 275 μg/ml for 4 or more weeks. A single patient treated at 215 μg/ml for 8 weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and no patient treated at 175 μg/ml developed this toxicity. The second most common toxicity observed was infection of the central venous catheter. The overall response rate for all of the evaluable patients was 17% (13 of 75 patients). In addition, prostate-specific antigen (PSA)-defined responses were observed in six patients receiving therapy at 175 μg/ml, but these responses were confounded by cessation of therapy with flutamide during suramin treatment. Conclusions: In summary, although plasma suramin concentrations were maintained below 300 μg/ml, neurologic toxicity nonetheless occurred with high frequency in patients treated at 275 μg/ml for 4 or more weeks. Therapy at 215 and 175 μg/ml was in general well tolerated, but central venous catheter-related infection, as well as the inconvenience and expense of continuous infusional therapy, make this method of drug delivery impractical. Only moderate antitumor activity was observed during this trial, but it is possible that both continuation of flutamide and flutamide withdrawal during suramin therapy confounded the assessment of suramin’s activity in hormone-refractory prostate cancer. Received: 9 June 1995/Accepted: 18 March 1996